# US 2018/0022699 A1 · Aryl substituted indoles and the use thereof

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- Number: US 2018/0022699 A1
- Document ID: US20180022699A1
- Status: Published application
- Kind: A1
- Application number: 15/669,193
- Filed: 2017-08-04
- Published: 2018-01-25
- Earliest claimed: 2010-06-16
- Assignees: Purdue Pharma L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Donald J. Kyle; Chiyou Ni; Laykea Tafesse; Jiangchao Yao
- Web page: https://patentgrep.com/patent/US20180022699A1

## CPC

- C07D 209/20: substituted additionally by nitrogen atoms, e.g. tryptophane
- A61P 9/06: Antiarrhythmics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/16: Otologicals
- C07B 59/002: {Heterocyclic compounds}
- C07D 209/12: Radicals substituted by oxygen atoms
- C07D 209/14: Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D 209/16: Tryptamines
- C07D 209/18: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 231/56: Benzopyrazoles; Hydrogenated benzopyrazoles
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 471/04: Ortho-condensed systems
- G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics}
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to aryl and heteroaryl substituted compounds of Formula (I), and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein G, R1, and Z1-Z5 are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain.

## Claims

### Claim at position 1

1-60. (canceled)

### Claim 61

A compound of Formula XV:
or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein
R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, haloalkoxyalkyl, aminoalkyl, alkylaminoalkyl, and dialkylaminoalkyl; and
R14, R15, R16, and R17 are, each independently, selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, haloalkyl, hydroxyalkyl, hydroxy, nitro, amino, cyano, amide, carboxyalkyl, alkoxyalkyl, ureido, acylamino, thiol, acyloxy, azido, alkoxy, carboxy, and aminocarbonyl.

### Claim 62

(canceled)

### Claim 63

A compound of an one of Formula XVII:
or a pharmaceutically acceptable salt, prodrug, or solvate thereof;
R14, R15, R16, and R17 are, each independently, selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halogen, haloalkyl, hydroxyalkyl, hydroxy, nitro, amino, cyano, amide, carboxyalkyl, alkoxyalkyl, ureido, acylamino, thiol, acyloxy, azido, alkoxy, carboxy, and aminocarbonyl.

### Claim at position 5

64-74. (canceled)

### Claim 75 (depends on 61)

A pharmaceutical composition, comprising the compound of claim 61, or a pharmaceutically acceptable salt, prodrug or solvate thereof, and a pharmaceutically acceptable carrier.

### Claim at position 7

76-79. (canceled)

### Claim 80 (depends on 61)

A method for treating pain in a mammal, comprising administering an effective amount of a compound as claimed in claim 61 or a pharmaceutically acceptable salt, prodrug or solvate thereof, to a mammal in need of such treatment.

### Claim 81

(canceled)

### Claim 82 (depends on 80)

The method of claim 80, wherein the method is for preemptive or palliative treatment of pain.

### Claim 83 (depends on 80)

The method of claim 80, wherein said pain is selected from the group consisting of chronic pain, inflammatory pain, neuropathic pain, postsurgical pain, acute pain, and surgical pain.

### Claim 84 (depends on 61)

A method of modulating sodium channels in a mammal, comprising administering to the mammal at least one compound as claimed in claim 61 or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein Nav1.7 sodium channel is modulated.

### Claim 85

(canceled)

### Claim 86 (depends on 61)

A compound as claimed in claim 61, wherein the compound is 3H, 11C, or 14C radiolabeled, or a pharmaceutically acceptable salt, prodrug or solvate thereof.

### Claim at position 15

87-91. (canceled)

### Claim 92 (depends on 63)

A pharmaceutical composition, comprising the compound of claim 63, or a pharmaceutically acceptable salt, prodrug or solvate thereof, and a pharmaceutically acceptable carrier.

### Claim 93 (depends on 63)

A method for treating pain in a mammal, comprising administering an effective amount of a compound as claimed in claim 63 or a pharmaceutically acceptable salt, prodrug or solvate thereof, to a mammal in need of such treatment.

### Claim 94 (depends on 93)

The method of claim 93, wherein said pain is selected from the group consisting of chronic pain, inflammatory pain, neuropathic pain, postsurgical pain, acute pain, and surgical pain.

### Claim 95 (depends on 63)

A compound as claimed in claim 63, wherein the compound is 3H, 11C, or 14C radiolabeled, or a pharmaceutically acceptable salt, prodrug or solvate thereof.

### Claim 96

A compound selected from the group consisting of
2-amino-3-[5-(4-phenoxyphenyl)-1H-indol-3-yl]propionamide;
2-amino-3-(5-(4-phenoxyphenyl)-1H-indol-3-yl)propan-1-ol;
2-amino-3-[6-(4-phenoxyphenyl)-1H-indol-3-yl]propionamide;
2-amino-3-[7-(4-phenoxyphenyl)-1H-indol-3-yl]propan-1-ol;
2-(1-(2-(diethylamino)ethyl)-5-(4-(4-fluorophenoxy)phenyl)-1H-indol-3-yl)-2-hydroxyacetamide;
(2S,2'S)-3,3′-(5-(4-(4-fluorophenoxy)phenyl)-1H-indole-1,3-diyl)bis(propane-1,2-diol);
(S)-3-(1-(2-(diethylamino)ethyl)-5-(4-(4-fluorophenoxy)phenyl)-1H-indol-3-yl)propane-1,2-diol;
(S)-2-(3-(2,3-dihydroxypropyl)-5-(4-(4-fluorophenoxy)phenyl)-1H-indol-1-yl)acetamide; and
(S)-3-(5-(4-(4-fluorophenoxy)phenyl)-1-(2-hydroxyethyl)-1H-indol-3-yl)propane-1,2-diol;
or a pharmaceutically acceptable salt, prodrug or solvate thereof, and a pharmaceutically acceptable carrier.

### Claim 97 (depends on 96)

A pharmaceutical composition, comprising the compound of claim 96, or a pharmaceutically acceptable salt, prodrug or solvate thereof, and a pharmaceutically acceptable carrier.

### Claim 98 (depends on 96)

A method for treating pain in a mammal, comprising administering an effective amount of a compound as claimed in claim 96 or a pharmaceutically acceptable salt, prodrug or solvate thereof, to a mammal in need of such treatment.